Pax2 expression and retinal morphogenesis in the normal and Krd mouse.
The Kidney and retinal defects (Krd) mouse carries a 7-cM transgene-induced deletion on chromosome 19 that includes the Pax2 locus. Adult mice heterozygous for the Krd deletion (Krd/+) are haploid for Pax2 and have a variable, semidominant phenotype characterized by structural defects of the kidney, retina, and optic disc. Renal and ocular anomalies present in heterozygous Pax2 mutants in both mice and humans support the hypothesis that haploinsufficiency of Pax2 underlies the Krd phenotype. To understand the embryonic basis of ocular defects observed in adult Krd/+ mice, we used immunohistochemistry, digital three-dimensional reconstructions, and quantitative morphometry to examine Pax2 protein distribution and ocular development in normal and Krd/+ mice from E10.5 to P2. In +/+ embryos, Pax2 immunopositive (Pax2+) cells demarcate the embryonic fissure as it forms in the ventral optic cup and optic stalk. After closure of the embryonic fissure, Pax2 immunostaining disappears from the ventral retina, but persists in a cuff of cells encircling the developing optic disc, the site where ganglion cell axons exit the retina. In Krd/+ embryos, Pax2+ cells in the posterior optic cup and the optic stalk undergo abnormal morphogenetic movements and the embryonic fissure fails to form normally. This results in an abnormal organization of the Pax2+ cells and ganglion cell axons at the nascent optic disc. The abnormal morphogenetic movements of the Pax2+ cells in the embryonic retina and optic stalk and the initial misrouting of the ganglion cell axons give rise to retinal and optic disc defects observed in the adult Krd/+ mice.
Otteson
D C
DC
Department of Anatomy and Cell Biology, University of Michigan, Ann Arbor 48105, USA.
Shelden
E
E
Jones
J M
JM
Kameoka
J
J
Hitchcock
P F
PF
D000818:Animals; D004268:DNA-Binding Proteins / Q000032:analysis / Q000096:biosynthesis* / Q000235:genetics; D007150:Immunohistochemistry; D007668:Kidney / Q000002:abnormalities / Q000196:embryology; D051379:Mice; D008810:Mice, Inbred C57BL; D008822:Mice, Transgenic; D009024:Morphogenesis / Q000235:genetics*; D009898:Optic Disk / Q000002:abnormalities / Q000737:chemistry / Q000196:embryology; D009900:Optic Nerve / Q000002:abnormalities / Q000737:chemistry / Q000196:embryology; D051762:PAX2 Transcription Factor; D012160:Retina / Q000002:abnormalities / Q000196:embryology*; D013194:Staining and Labeling; D014157:Transcription Factors / Q000032:analysis / Q000096:biosynthesis* / Q000235:genetics
D004268:DNA-Binding Proteins; D051762:PAX2 Transcription Factor; C497319:Pax2 protein, mouse; D014157:Transcription Factors